This invention is based on a published work by the inventors: “Integrated Measurement of the Mass and Surface Charge of Discrete Microparticles Using a Suspended Microchannel Resonator;” Philip Dextras, Thomas P. Burg and Scott R. Manalis; Anal. Chem., 2009, 81 (11), pp 4517-4523; Publication Date (Web): May 8, 2009 (Article); DOI: 10.1021/ac9005149. The contents of this article are incorporated in their entirety by reference. The invention relates to utilizing the high-resolution particle measurement capabilities of a Suspended Miccrochannel (SMR) resonator in combination with an applied oscillating electric field to provide an unprecedented single particle characterization capability
Colloidal dispersions have a broad range of technological applications, including paints, pharmaceuticals, foods, photographic emulsions, ceramics, drilling muds, inks, and photonic crystals. Many of these applications require very precise control over colloidal stability and hence inter-particle interactions which are dependent on the physico-chemical properties of the particles themselves. Quantitative measures of particle properties such as the size, mass and surface charge are therefore often of value in designing systems and manufacturing processes for these applications. Measurements of particle size and surface charge are routinely performed using light scattering techniques such as phase analysis light scattering (PALS). This technique estimates the size and electrophoretic mobility of particles by measuring their average Brownian motion and their motion in an applied electric field respectively. While applicable to a wide variety of colloidal systems, PALS reports size and mobility values which represent averages over multiple particles. Hence accuracy in estimating the particle's charge, which is dependent on both the size and the mobility, can suffer from errors made in ensemble average measurements of these two parameters, both of which may be multi-modal for a complex population.
Various approaches for measuring size and electrical properties of single particles have been explored, such as the Coulter principle and mass spectrometry. Carbon nanotube-based Coulter counters are able to measure discrete-particle mobility and size, but compromises must be made between the signal-to-noise ratio (SNR) of the mobility measurement and that of the size measurement since they have inherently different optimum orifice lengths. Measurement of particle charge-to-mass ratio by time-of-flight mass spectrometry has been integrated with direct charge measurement using a Faraday disc, but because the sample must be dried, the measured charge may not accurately reflect that experienced in the desired dispersion medium for a given application.
Relatively recently, particle detection and measurement based on the use of SMR's has been developed, and shows promise of going beyond some of the limitations of conventional techniques. The SMR uses a fluidic microchannel embedded in a resonant structure, typically in the form of a cantilever or torsional structure. Fluids, usually containing target particles are flowed through the sensor, and the contribution of the flowed material to the total mass within the sensor causes the resonance frequency of the sensor to change in a measurable fashion. SMR's are typically microfabricated MEMS devices. The use of microfabricated resonant mass sensors to measure fluid density has been known in the literature for some time [P. Enoksson, G. Stemme, E. Stemme, “Silicon tube structures for a fluid-density sensor”, Sensors and Actuators A 54 (1996) 558-562]. However, the practical use of resonant mass sensors to measure properties of individual particles and other entities suspended in fluid is relatively recent, as earlier fluid density sensors were not designed to measure individual particles at the micron and submicron scale.
In a body of work by common inventors and owned by the assignee of the current application, miniaturization and improvement of several orders of magnitude in mass resolution has been demonstrated. Development in the microfabrication recipes, the fluidics design, and measurement techniques are described in a number of co-pending patent applications and scientific publications. Of particular relevance is a publication by some of the current inventors, [T. P. Burg, M. Godin, S. M. Knudsen et al., “Weighing of biomolecules, single cells and single nanoparticles in fluid,” Nature 446 (7139), 1066-1069 (2007)] By using the microfabrication techniques described in the references, SMR sensors have been fabricated with mass resolution of less than 1 femtogram (10−15 g). This resolution is sufficient to detect and measure the mass of individual particles in the range of ˜100 nanometers up to many microns in size, including mammalian cells. In addition, as the particle transits the SMR, the resonance frequency of the SMR is highly sensitive to its position along the SMR channel.
As SMR based techniques overcome some of the disadvantages of the prior art in terms of individual particle characterization, it would be desirable to utilize the measurement capabilities of an SMR to finely characterize mass and position and extend the range of particle characterization. In particular it is the object of this invention to provide an SMR based technique that also yields single micro-particle surface charge in addition to mass and density characterization.